Cited by 58Cellular transport and secretionProtease and Inhibitor MechanismsBlood Coagulation and Thrombosis Mechanisms

The mosaic receptor sorLA/LR11 binds components of the plasminogen-activating system and platelet-derived growth factor-BB similarly to LRP1 (low-density lipoprotein receptor-related protein), but mediates slow internalization of bound ligand

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GLIEMANN, Jørgen, HERMEY, Guido, NYKJÆR, Anders, PETERSEN, Claus M., JACOBSEN, Christian, ANDREASEN, Peter A.·2004·Biochemical Journal

Abstract

The type-1 receptor sorLA/LR11, a member of the Vps10p-domain receptor family that also contains domains characterizing members of the LDL (low-density lipoprotein) receptor family, has been shown to induce increased uPAR (urokinase receptor) expression as well as enhanced migration and invasion activities in smooth muscle cells in the presence of PDGF-BB (platelet-derived growth factor-BB). Here we show that sorLA interacts with both components of the plasminogen activating system and PDGF-BB similarly to LRP1 (LDL receptor-related protein/α2-macroglobulin receptor), which is an important clearance receptor with established functions in controlling uPAR expression as well as PDGF-BB signalling. In contrast with LRP1, sorLA does not interact with α2-macroglobulin, which is a binding protein for several growth factors, including PDGF-BB. By using LRP1-deficient cells transfected with sorLA, we demonstrate that sorLA-bound ligand is internalized at a much lower rate than LRP1-bound ligand, and that sorLA is inefficient in regulating cell surface uPAR expression, which depends on rapid internalization of the ternary complex between urokinase-type plasminogen activator, its type-1 inhibitor, and uPAR. Thus, although overlapping with regard to binding profiles, sorLA is substantially less efficient as a clearance receptor than LRP1. We propose that sorLA can divert ligands away from LRP1 and thereby inhibit both their clearance and signalling events mediated by LRP1.

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Crossref · 10.1042/bj20040149

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  • SORL1, a vacuolar protein sorting-10 domain-containing protein, binds PDGF-BB and LRP1 ligands.

    “SORL1, a vacuolar protein sorting-10 (Vps10) domain-containing protein, binds PDGF-BB (205, 247) and LRP1 ligands (205).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [205]

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Authors
GLIEMANN, J., HERMEY, G., NYKJÆR, A., PETERSEN, C. M., JACOBSEN, C., & ANDREASEN, P. A.
Affiliations
Aarhus University (DK)
Corresponding author
  • HERMEY, Guido
  • JACOBSEN, Christian
Venue
Biochemical Journal
Published
2004-06-22
Volume
381
Issue
1
Pages
203-212
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
OpenAlex
W2069281240
Cited by
58
References
50
Citations by year
2026: 2 · 2025: 3 · 2024: 2 · 2022: 3 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 1 · 2013: 3
FWCI
2.16
Type
journal article
Language
en
Open access
Locations
  • Biochemical Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Sundhed og Sygdom, Det Frie Forskningsråd
  • Novo Nordisk Fonden
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
LRP1, urokinase receptor, uPAR, PDGF-BB, LDL receptor family, ligand internalization, alpha2-macroglobulin
MeSH terms
Becaplermin, alpha-Macroglobulins, Animals, Cell Line, Endocytosis, Cricetinae, Humans, Ligands, Platelet-Derived Growth Factor, Receptors, Cell Surface, Receptors, LDL, Transfection, CHO Cells, Proto-Oncogene Proteins c-sis, LDL-Receptor Related Proteins, Low Density Lipoprotein Receptor-Related Protein-1, LDL-Receptor Related Protein-Associated Protein, Membrane Transport Proteins, Receptors, Urokinase Plasminogen Activator

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